Alterations in Immune Response Profile of Tumor-Draining Lymph Nodes after High-Intensity Focused Ultrasound Ablation of Breast Cancer Patients.

Previous studies have revealed that high-intensity focused ultrasound (HIFU) ablation can trigger an antitumor immune response. The aim of this study was to investigate immune response in tumor-draining lymph nodes (TDLNs) after HIFU treatment. Forty-eight female patients with biopsy-confirmed breast cancer were divided into a control group and an HIFU group. In the control group, 25 patients underwent modified radical mastectomy, but 23 patients in the HIFU group received HIFU ablation of primary cancer, followed by the same operation. Using HE and immunohistochemical staining, the immunologic reactivity pattern and immune cell profile were assessed in paraffin-embedded axillary lymph nodes (ALNs) in all patients. The results showed that ALNs presented more evident immune reactions in the HIFU group than in the control group (100% vs. 64%). Among the ALNs, 78.3% had mixed cellular and humoral immune response, whereas 36% in the control group showed cellular immune response. The numbers of CD3+, CD4+, NK cell, and activated CTLs with Fas ligand+, granzyme+ and perforin+ expression were significantly higher in the ALNs in the HIFU group. It was concluded that HIFU could stimulate potent immune response and significantly increase T cell, activated CTLs and NK cell populations in the TDLNs of breast cancer.

[Cu30I16(mtpmt)12(µ(10-S4))]: an unusual 30-membered copper(I) cluster derived from the C-S bond cleavage and its use in heterogeneous catalysis.

The Cu(I)-mediated C-S bond cleavage of 5-methyl-4-(p-tolyl)pyrimidine-2-thiol (mtpmtH) gave one 30-nuclear cluster [Cu30I16(mtpmt)12(µ10-S4)], one polymeric complex [(bmtpms)Cu-(µ-I)]n and one tetranuclear complex [(bmptmds){Cu(µ-I)}2]2; the 30-nuclear cluster displayed excellent catalytic performances in the coupling reactions of N-heterocycles and arylboronic acids and could be recycled and reused.

[Water storage capacity of qinghai spruce (Picea crassifolia) forest canopy in Qilian Mountains].

By the methods of direct measurement and regression analysis, this paper estimated the water storage capacity of Picea crassifolia forest canopy in Guantan in Qilianshan Mountains, based on the observed throughfall and the laboratory experimental data about the water storage capacity of various canopy components in 2008. Due to the impacts of various factors, differences existed in the canopy water storage capacity estimated by the two methods. The regression analysis was mainly impacted by the measurement approaches of the throughfall, the maximum water storage capacity estimated being 0.69 mm, whereas the direct measurement was mainly impacted by tree height, diameter at breast height, plant density, and leaf area index, with the estimated maximum water storage capacity being 0.77 mm. The direct measurement showed that the maximum water storage capacity per unit area of the canopy components of the forest was in the order of barks (0.31 mm) > branches (0.28 mm) > leaves (0.08 mm).

[Spatial distribution characteristics of the biomass and carbon storage of Qinghai spruce (Picea crassifolia) forests in Qilian Mountains].

This paper estimated the biomass and carbon storage and their spatial distributions of Qinghai spruce (Picea crassifolia) forests in Qilian Mountains, based on the field investigation, forest map, and meteorological data, and with the help of GIS technology. In 2008, the biomass of the forests was averagely 209.24 t x hm(-2), with a total biomass of 3.4 x 10(7) t. Due to the difference of water and thermal condition, there existed great differences in the biomass of Qinghai spruce within the Mountains. The biomass increased by 3.12 t x hm(-2) with increasing 1 degrees longitude and decreased by 3.8 t x hm(-2) with increasing 1 degrees latitude, and decreased by 0.05 t x hm(-2) with the elevation increasing 100 m. The carbon density of the forests ranged from 70.4 to 131.1 t x hm(-2), averagely 109.8 t x hm(-2), and the average carbon density was 83.8 t x hm(-2) for the young forest, 109.6 t x hm(-2) for the middle age forest, 122 t x hm(-2) for the near-mature forest, 124.2 t x hm(-2) for the mature forest, and 117.1 t x hm(-2) for the over-mature forest. The total carbon storage of Qinghai spruce forests in the study area was 1.8 x 10(7) t.

[Spatial distribution of Tamarix ramosissima aboveground biomass and water consumption in the lower reaches of Heihe River, Northwest China].

Based on the field observation on the Tamarix ramosissima populations in the lower reaches of Heihe River, the relationship models between the aboveground biomass of T. ramosissima and its morphological features (basal diameter, height, and canopy perimeter) were built. In the mean time, the land use/cover of the study area was classified by the decision tree classification with high resolution image (QuickBird), the distribution of T. ramosissima was extracted from classification map, and the morphological feature (canopy perimeter) of T. ramosissima was calculated with ArcGIS 9.2. On the bases of these, the spatial distribution of T. ramosissima aboveground biomass in the study area was estimated. Finally, the spatial distribution of the water consumption of T. ramosissima in the study area was calculated by the transpiration coefficient (300) and the aboveground biomass. The results showed that the aboveground biomass of T. ramosissima was 69644.7 t, and the biomass per unit area was 0.78 kg x m(-2). Spatially, the habitats along the banks of Heihe River were suitable for T. ramosissima, and thus, this tree species had a high biomass. The total amount of water consumption of T. ramosissima in the study area was 2.1 x 10(7) m3, and the annual mean water consumption of T. ramosissima ranged from 30 mm to 386 mm.

Increased infiltration of activated tumor-infiltrating lymphocytes after high intensity focused ultrasound ablation of human breast cancer.

BACKGROUND: Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can induce a distinct inflammatory reaction with marked infiltration of lymphocytes after direct tumor destruction. In this study, we investigated the status of tumor-infiltrating lymphocytes (TILs) after HIFU ablation of human breast cancer and explored mechanisms that may be involved in HIFU-triggered, antitumor immune response. METHODS: A total of 48 female patients with biopsy-proven breast cancer were divided randomly into 1 of 2 groups: control group (n = 25), in which only modified radical mastectomy was performed, or HIFU group (n = 23), in which HIFU ablation of the primary breast cancer was performed prior to modified radical mastectomy. Using semiquantitative immunohistochemical analysis, tumor-infiltrating T lymphocytes and subsets, B lymphocytes, and natural killer (NK) cells were assessed in all patients. Expression of Fas ligand (FasL), granzyme, and perforin on TILs was also studied in both groups. RESULTS: TILs infiltrated along the margins of the ablated region in all HIFU-treated neoplasms, and the numbers of tumor-infiltrating CD3, CD4, CD8, CD4/CD8, B lymphocytes, and NK cells was increased significantly in the HIFU group. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly greater in the HIFU group than in the control group. CONCLUSION: HIFU ablation induced marked infiltration of CD3, CD4, CD8, B lymphocytes, and NK cells in the treated breast lesions. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly increased after HIFU treatment.

Activation of tumor-infiltrating antigen presenting cells by high intensity focused ultrasound ablation of human breast cancer.

Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can trigger activation of host antitumor responses after direct tumor destruction. The goal of this study was to investigate the status and functions of tumor-infiltrating antigen presenting cells (APCs) after HIFU ablation of human breast cancer, and to explore the mechanisms regarding HIFU-enhanced antitumor response. Forty-eight women with biopsy-proven breast cancer were divided randomly into a control group (n = 25) and a HIFU group (n = 23). Patients in the control group received modified radical mastectomy, and those in the HIFU group underwent HIFU ablation of primary breast cancer, followed by modified radical mastectomy within 1-2 weeks. Using immunohistochemical analysis, tumor-infiltrating dendritic cells (DCs), macrophages, B lymphocytes and expression of HLA-DR and costimulatory molecules on DCs and macrophages were assessed in all patients. The results showed that APCs infiltrated along the margins of the ablated regions in all HIFU-treated tumors, and numbers of tumor-infiltrating DCs, macrophages and B lymphocytes increased significantly in the HIFU group. Compared with the values in the control group, the percentage of DCs and macrophages expressing HLA-DR, CD80 and CD86 was significantly greater in the HIFU group. There were statistically significant differences between numbers of S-100(+) HLA-DR(+), S-100(+) CD80(+), S-100(+) CD86(+), CD68(+) HLA-DR(+), CD68(+) CD80(+) and CD68(+) CD86(+) cells in the control and HIFU groups, respectively. It was concluded that HIFU ablation induces significant infiltration of APCs within the residual tumor debris in patients with breast cancer, and most of the tumor-infiltrating DCs and macrophages were activated after HIFU ablation.

Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment.

Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor-secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients.

Expression of tumor antigens and heat-shock protein 70 in breast cancer cells after high-intensity focused ultrasound ablation.

BACKGROUND: Previous results have shown that high-intensity focused ultrasound (HIFU) ablation can potentially activate a host antitumor immunity. The goal of this study was to investigate whether the tumor antigens expressed on breast cancer cells may be preserved after HIFU treatment, and to explore the potential mechanisms regarding the enhanced antitumor response. METHODS: The primary lesion in 23 patients with biopsy-proven breast cancer were treated with HIFU, then submitted to modified radical mastectomy. By using biotin-streptavidin-peroxidase immunohistochemical technology, a variety of cellular molecules expressed on breast cancer cells, including tumor antigens and heat-shock protein 70 (HSP-70), were stained in all breast specimens. A complete absence of staining was recorded as negative, and immunoreaction of the tumor cells was considered to be positive for antigen expression. RESULTS: Nuclear positivity of breast cancer cells for proliferating cell nuclear antigen, estrogen receptor, and progesterone receptor was detected in 0%, 9%, and 9% of the treated samples, respectively. The positive rate of cytoplasmic staining for matrix metalloproteinase 9, carbohydrate antigen 15-3, vascular endothelial growth factor, transforming growth factors beta1 and beta2, interleukin 6, and interleukin 10 was 0%, 52%, 30%, 57%, 70%, 48%, and 61% in the treated cancer cells, respectively. The positive rate of cellular membrane staining for epithelial membrane antigen, CD44v6, and HSP-70 was 100%, 0%, and 100% in the zones of treated cancer cells, respectively. CONCLUSIONS: After HIFU ablation, some tumor antigens remained in the tumor debris. This could provide a potential antigen source to stimulate antitumor immune response.

Heat fixation of cancer cells ablated with high-intensity-focused ultrasound in patients with breast cancer.

BACKGROUND: High-intensity-focused ultrasound (HIFU) is a noninvasive thermal ablation technique. This study reports the use of histological techniques for the pathological assessment of HIFU effects in patients with breast cancer. METHODS: Twenty-three patients with biopsy-proven breast cancer underwent HIFU treatment for primary breast lesion. Mastectomy was performed on all patients after HIFU. By using histological examinations, the surgical specimens were assessed to explore HIFU effects on breast cancer. RESULTS: Coagulation necrosis of targeted tumors was confirmed by microscopy in 23 patients. Tumor cells presented typical characteristics of coagulation necrosis in the peripheral region of the ablated tumor in all patients. However, in 11 of 23 patients, hematoxylin and eosin staining showed normal cellular structure in the central ablated tumor. By using electronic microscopy and nicotinamide adenine dinucleotide-diaphorase stain, those who had normal-appearing cancer cells were not viable. CONCLUSIONS: HIFU can cause the heat fixation of ablated tumor through thermal effect.